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| {{STRUCTURE_1x1s| PDB=1x1s | SCENE= }} | | {{STRUCTURE_1x1s| PDB=1x1s | SCENE= }} |
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| '''Crystal structure of M-Ras in complex with GppNHp'''
| | ===Crystal structure of M-Ras in complex with GppNHp=== |
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| ==Overview==
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| Although some members of Ras family small GTPases, including M-Ras, share the primary structure of their effector regions with Ras, they exhibit vastly different binding properties to Ras effectors such as c-Raf-1. We have solved the crystal structure of M-Ras in the GDP-bound and guanosine 5'-(beta,gamma-imido)triphosphate (Gpp(NH)p)-bound forms. The overall structure of M-Ras resembles those of H-Ras and Rap2A, except that M-Ras-Gpp(NH)p exhibits a distinctive switch I conformation, which is caused by impaired intramolecular interactions between Thr-45 (corresponding to Thr-35 of H-Ras) of the effector region and the gamma-phosphate of Gpp(NH)p. Previous 31P NMR studies showed that H-Ras-Gpp(NH)p exists in two interconverting conformations, states 1 and 2. Whereas state 2 is a predominant form of H-Ras and corresponds to the "on" conformation found in the complex with effectors, state 1 is thought to represent the "off" conformation, whose tertiary structure remains unknown. 31P NMR analysis shows that free M-Ras-Gpp(NH)p predominantly assumes the state 1 conformation, which undergoes conformational transition to state 2 upon association with c-Raf-1. These results indicate that the solved structure of M-Ras-Gp-p(NH)p corresponds to the state 1 conformation. The predominance of state 1 in M-Ras is likely to account for its weak binding ability to the Ras effectors, suggesting the importance of the tertiary structure factor in small GTPase-effector interaction. Further, the first determination of the state 1 structure provides a molecular basis for developing novel anti-cancer drugs as compounds that hold Ras in the state 1 "off" conformation.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15994326}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15994326 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15994326}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Ye, M.]] | | [[Category: Ye, M.]] |
| [[Category: Gtp-binding]] | | [[Category: Gtp-binding]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:25:16 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 16:31:08 2008'' |
